TLR4/NF-κB通路在慢性鼻-鼻窦炎伴鼻息肉和不伴鼻息肉的黏膜上皮修复机制中的作用  

The Role of TLR4/NF-κB Signaling Pathway in the Repair of Mucosal Epithelium in Chronic Sinusitis with Nasal Polyps and Without Nasal Polyps

作　　者：刘亮亮[1] 文华[2] 杨瑾[3] 卢媛媛[1] 王正辉[4] LIU Liang-liang;WEN Hua;YANG Jin;LU Yuan-yuan;WANG Zheng-hui(Department of Ophthalmology,Otolaryngology,Xi'an Jiaotong University Hospital,Xi'an 710049,Shaanxi,China;Public Health Center of Xi'an Jiaotong University Hospital,Xi'an 710049,Shaanxi,China;Department of Obstetrics and Gynecology,Xi'an Jiaotong University Hospital,Xi'an 710049,Shaanxi,China;Department of Otolaryngology,the Second Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710004,Shaanxi,China)

机构地区：[1]西安交通大学医院眼耳鼻咽喉科,陕西西安710049 [2]西安交通大学医院公共卫生中心,陕西西安710049 [3]西安交通大学医院妇产科,陕西西安710049 [4]西安交通大学第二附属医院耳鼻咽喉头颈外科病院,陕西西安710004

出　　处：《医学信息》2022年第15期39-45,共7页Journal of Medical Information

摘　　要：目的探讨TLR4/NF-κB通路在慢性鼻-鼻窦炎(CRS)伴鼻息肉(CRSwNP)和不伴鼻息肉(CRSsNP)的黏膜上皮修复机制中的作用。方法收集2018年3月-2021年9月就诊于西安交通大学附属医院耳鼻咽喉科的30例CRS患者的鼻筛窦黏膜上皮组织。将CRS患者组织分为CRSsNP组和CRSwNP组,每组10例。对照组组织来源于进行视觉性鼻整形术的患者。HE染色、免疫组化法检测各组患者鼻黏膜组织病理学改变以及TLR4、NF-κB的表达;将各组鼻粘膜上皮细胞进行离体培养,分别以4种因素(空白对照组;EGF组:添加50 ml 5 ng/ml EGF;TLR4/NF-κB组:依次添加5 ng/ml TLR4和NF-κB培养24 h后,添加5 ng/ml EGF;PDTC组:添加5 ng/ml信号通路抑制剂PDTC培养12 h后,添加5 ng/ml TLR4和NF-κB培养12 h后,添加5 ng/ml EGF)刺激各组鼻粘膜上皮细胞,CCK-8法、ELISA检测各组鼻黏膜上皮细胞的增殖以及IL-β、1L-5的表达。结果与CRSsNP组相比,CRSwNP组的鼻窦CT评分明显升高(P<0.05);与对照组患者相比,CRSsNP组、CRSwNP组TLR4、NF-κB的表达量升高(P<0.05);与CRSsNP组相比,CRSwNP组TLR4、NF-κB的表达量升高(P<0.05);CCK-8和ELISA法实验结果:与对照组相比,CRS组鼻粘膜上皮细胞的增殖基线降低,IL-β、IL-5的水平升高(P<0.05);与CRSsNP组相比,CRSwNP组鼻粘膜上皮细胞的增殖基线升高,IL-β、IL-5的水平升高(P<0.05);对照组和CRS组加入EGF后,与空白对照相比,鼻粘膜上皮细胞的增殖基线明显升高,IL-β、IL-5的水平降低(P<0.05);加入TLR4和NF-κB后,与空白对照相比,鼻粘膜上皮细胞的增殖基线降低,IL-β、IL-5的水平升高(P<0.05);加入PDTC后,EGF诱导细胞增值的作用明显有所恢复,IL-β、IL-5的水平明显有所降低(P<0.05)。结论TLR4/NF-κB信号通路影响CRS中CRSsNP和CRSwNP两者鼻粘膜上皮细胞损伤后的修复,抑制TLR4/NF-κB信号通路能明显增强CRS患者鼻粘膜上皮细胞的增殖作用。Objective To investigate the role of TLR4/NF-κB pathway in the repair of mucosal epithelium in chronic rhinosinusitis(CRS)with nasal polyps(CRSwNP)and chronic rhinosinusitis without nasal polyps(CRSsNP).Methods The nasal ethmoid sinus mucosal epithelial tissues of 30 patients with CRS were collected from the Department of Otolaryngology,Affiliated Hospital of Xi'an Jiaotong University from March 2018 to September 2021.The tissues of CRS patients were divided into CRSsNP group and CRSwNP group,with 10 cases in each group.The control group was derived from patients undergoing visual rhinoplasty.HE staining and immunohistochemistry were used to detect the pathological changes of nasal mucosa and the expressions of TLR4 and NF-κB in each group.The nasal epithelial cells of each group were cultured in vitro with four factors blank control group;eGF group:adding 50 ml 5 ng/ml EGF;TLR4/NF-κB group:5 ng/ml EGF was added after TLR4 and NF-κB were cultured for 24 h;PDTC group:After PDTC with 5 ng/ml signal pathway inhibitor was added for 12 h,TLR4 with 5 ng/ml and NF-κB were added for 12 h,and EGF with 5 ng/ml was added to stimulate nasal epithelial cells in each group.CCK-8 method and ELISA were used to detect the proliferation of nasal epithelial cells and the expression of IL-βand IL-5 in each group.Results Compared with CRSsNP group,the CT score of sinus in CRSwNP group was significantly increased(P<0.05).Compared with the control group,the expression of TLR4 and NF-κB in CRSsNP group and CRSwNP group increased(P<0.05).Compared with CRSsNP group,the expression of TLR4 and NF-κB in CRSwNP group increased(P<0.05).CCK-8 and ELISA results showed that compared with the control group,the proliferation baseline of nasal epithelial cells in CRS group was decreased,and the levels of IL-βand IL-5 were increased(P<0.05).Compared with CRSsNP group,the proliferation baseline of nasal epithelial cells in CRSwNP group was increased,and the levels of IL-βand IL-5 were increased(P<0.05).After EGF was added to the control grou

关 键 词：慢性鼻-鼻窦炎伴鼻息肉 慢性鼻-鼻窦炎不伴鼻息肉 黏膜上皮 TLR4/NF-κB信号通路 修复 

分 类 号：R765[医药卫生—耳鼻咽喉科]